Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions

作者：Nyitrai Gabriella^*; Kekesi Orsolya; Pal Ildiko; Keglevich Peter; Csiki Zsuzsanna; Fuegedi Peter; Simon Agnes; Fitos Ilona; Nemeth Krisztina; Visy Julia; Tarkanyi Gabor; Kardos Julianna

来源：Nanotoxicology, 2012, 6(6): 576-586.

DOI：10.3109/17435390.2011.591511

• Functional neurotoxicity indicators
• polycationic and polyanionic PAMAM dendrimers
• beta-D-glucopyranose-conjugation
• imaging cell death
• molecular simulation

We report for the first time on neuronal signaling for the evaluation of interactions between native plasmamembrane and polyamidoamine (PAMAM) dendrimers. Generation 5 polycationic (G5-NH2), novel beta-D-glucopyranose-conjugated G5-NH2 and generation 4.5 polyanionic (G4.5-COONa) polyamidoamine (PAMAM) dendrimers (1-0.0001 mg/ml) were applied in acute brain slices. Functional toxicity assessments-validated by fluorescence imaging of dead cells-were performed by employing electrophysiological indicators of plasma membrane breakdown and synaptic transmission relapse. Irreversible membrane depolarization and decrease of membrane resistance predicted substantial functional neurotoxicity of unmodified G5-NH2, but not of the G4.5-COONa PAMAM dendrimers. Model calculations suggested that freely moving protonated NH2 groups of terminal monomeric units of PAMAM dendrimers may be able directly destroy the membrane or inhibit important K+ channel function via contacting the positively charged NH2. In accordance, conjugation of surface amino groups by beta-D-glucopyranose units reduced functional neurotoxicity that may hold great potential for biomedical applications.

• 出版日期2012-9